We have demonstrated that collagenase digestion of islets damage the surface receptors which will regenerate in tissue culture and then render the islets superior as implantation material. Concanavalin A(Con A) was used as a probe to examine beta cell membrane characteristics. In addition a culture technique for the long-term preservation of islets in vitro was developed. Our objectives are to expand on these observations and the following experiments are planned. 1) culture-maintained islets will be used as implantation source for grafting of both the chronic and the severely diabetic rat. 2) Con A coated islets will be investigated further and functional characteristics and ability to reverse the diabetic process in both the syngeneic and the allogeneic host will be determined. 3) Attempts will be made to transplant islets into allogeneic hosts. Two approaches will be followed: a) induction of tolerance to a crude extract of islets with the use of an immunosuppressive agent and b) solubilization of histocompatibility antigens from one strain of rat and induction of tolerance to these in a different strain of rat prior to transplantation of endocrine pancreas. The latter procedure will hopefully not require the use of an immunosuppressive agent.